Effects of dexamethasone on airway hyper-responsiveness to the adenosine A(1) receptor agonist cyclo-pentyl adenosine in an allergic rabbit model

1 New Zealand White (NZW) rabbits were immunized within 24 h of birth with Alternaria tenuis in aluminium hydroxide (Al (OH)(3)) (i.p.) or sham immuni zed (saline plus Al (OH)(3) i.p.) and subsequently injected with the allerg en (i.p.) or sham-immunized for the next 3 months. At 3 months of age, base line airway responsiveness was assessed using cyclo-pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of p eripheral blood were collected from some animals for estimation of dexameth asone levels. In some animals, blood was collected at the end of the experi ment and cellular function was assessed by measurement of ex vivo prolifera tion of mononuclear cells in response to phytohaemagglutinin (PHA). 2 Allergen immunization significantly increased baseline airway responsiven ess to inhaled CPA (P < 0.05) in comparison with sham-immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg(-1) day(-1)) treatme nt for 1 month did not modify this established airway hyper-responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant p lasma levels of dexamethasone were achieved in dexamethasone treated animal s. 3 Treatment of rabbits with dexamethasone (0.1 mg kg(-1) i.p.), 6 h prior t o each allergen injection from the neonatal stage, significantly reduced ba seline airway hyper-responsiveness to CPA measured at 3 months (P < 0.05). There was no significant difference in either total or differential cell nu mbers in BAL fluid, or any difference in mitogen-induced proliferation of m ononuclear cells between dexamethasone and vehicle treated rabbits. 4 These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper-responsiveness to inhaled CPA in all ergic rabbits. However, once established, such underlying airway hyper-resp onsiveness is difficult to resolve, even with prolonged treatment with gluc ocorticosteroids.